Mitsunobu displacement reaction

In the olivanic acid series of carbapenems the ( )-acetamidoethenyl grouping can be isomerised to the (Z)-isomer (19) (22) and reaction with hypobromous acid provides a bromohydrin that fragments to give a thiol of type (20) when R = H, SO H, or COCH. The thiol is not isolated but can react to provide new alkyl or alkenyl C-2 substituents (28). In the case of the nonsulfated olivanic acids, inversion of the stereochemistry at the 8(3)-hydroxyl group by way of a Mitsunobu reaction affords an entry to the 8(R)-thienamycin series (29). An alternative method for introducing new sulfur substituents makes use of a displacement reaction of a carbapenem (3)-oxide with a thiol (30). Microbial deacylation of the acylamino group in PS-5 (5) has... 

The Mitsunobu reaction is used to convert an alcohol and an acid into an ester by the formation of an activated alcohol (Ph3P, diethyl diazodicar-boxylate), which then undergoes displacement with inversion by the carboxylate. Although this reaction works very well, it suffers from the fact that large quantities of by-products are produced, which generally require removal by chromatography. 

Isomerization of the enantiopure hydroxylated azepane 42, after hydroxyl group activation, afforded either the ring-contracted piperidine derivative 45 (on O-mesylation to 43 followed by internal displacement to the aziridinium ion intermediate 44 and subsequent chloride ion induced ring opening) or the chiral ethylene-bridged morpholines 48 via 47 and an intramolecular Mitsunobu reaction of 46 (Scheme 4) <1996TL1613>. 

This reaction is somewhat similar to the Mitsunobu Reaction, where the combination of a phosphine, a diazo compound as a coupling reagent, and a nucleophile are used to invert the stereochemistry of an alcohol or displace it. 

The Mitsunobu reaction has been successfully applied to the synthesis of carbohydrate epoxides directly from diols (Scheme 3.15c).84 The more accessible and nucleophilic hydroxyl is converted into an alkoxyphos-phonium ion, which in turn is intramolecularly displaced by a hydroxyl to give an epoxide. Again it is of critical importance that a coplanar SN2 transition state be attained. 

Macrolactonization can also be achieved by the Mitsunobu reaction [44] with inversion of the configuration of the alcohol. The reaction principle and mechanism are demonstrated in Scheme 24. Addition of triphenylphosphine to diethyl azodicarboxylate (DEAD, 73) forms a quaternary phosphonium salt 74, which is protonated by hydroxy acid 11, followed by phosphorus transfer from nitrogen to oxygen yielding the alkoxyphosphonium salt 76 and diethyl hydrazinedicarboxy-late 75. Then, an intramolecular Sn2 displacement of the important intermediate 76 results in the formation of the lactone 15 and triphenylphosphine oxide. 

O-Aryl glycidol ethers can be prepared from glycidol by the Mitsunobu reaction with phenols (see eq 3) and are also made from direct displacement by glycidol on activated haloaryls. ... 

The closure of the lactone must be done with inversion of configuration at the alcohol centre. We should normally use a Mitsunobu reaction for this but mesylation is a good alternative. Mesylatior occurs via the sulfene with retention and then displacement of this excellent leaving group require, inversion and the cis lactone is formed. 

The PTSO2 moiety is introduced either via an 8 2 displacement-oxidation sequence or by using the Mitsunobu reaction followed by oxidation, as shown below. ... 

This type is a one-pot reaction widi all components present fix>m the beginning. The alcohol is first converted into an 5N-activated (HGA) species (43), which undergoes an OX displacement with the carboxylic acid to form the ester (equation 18). Two methods are known to fit into this general scheme the Mitsunobu reaction and die Vorbriiggen-Eschenmoser reaction. ... 

Amines. Chiral a-amino acids are obtained from cyanohydrins via a Mitsunobu reaction employing A-f-butoxycarbonyl-A-(2-trimethylsilyl)ethylsulfonamide as the nucleophile. The a-aminonitrile derivatives thus generated are hydrolyzed with acid. By means of an intramolecular displacement (3-hydroxy acids are transformed into (3-amino acids. Thus, subjecting the derived 0-benzylhydroxamides to Mitsunobu reaction conditions leads to (3-lactams which are readily processed (LiOH H, Pd/C). 

The optimum conditions have been thoroughly worked out,318,431 although a direct comparison of the diastereodirecting efficiency of various oxazolidinones does not appear to have been made for animations. However, they all direct the incoming electrophile to the less hindered side of the Z-enolate as illustrated in Eqs. 127431 and 128.434 The diastereomer with the opposite configuration at the amination site can be obtained using the enantiomeric chiral auxiliary or from the same V-acy Ioxazolidinone by a bromination/SN2 displacement sequence (Eq. 129)431 or a hydroxylation/Mitsunobu reaction protocol.427... 

Caspi and co-workers (56) have reported the synthesis of n-octane containing a chiral methyl group by the displacement of the mesylate of (R)- and (S)-l-[l-3H]octanol with superdeuteride. A unique feature of their approach (56,57) was the chemical conversion of the more readily available tritiated IS alcohol, obtained from the reduction of [l-3H]octanal by horse liver alcohol dehydrogenase, to the more difficult-to-obtain 1/ alcohol by the Mitsunobu reaction. Using the conditions shown in Scheme 10, the (IS)-alcohol was converted to the (l/ )-benzoate which gave the (17 )-alcohol by reductive cleavage with LiAlH4. 

At this point, we investigated the reduction of the ketone to the phenethyl alcohol followed by Mitsunobu displacement as well as direct reductive amination. We were able to efficiently reduce the ketone racemically using NaBH4 in MeOH to alcohol 32. However, the subsequent Mitsunobu reaction proved problematic and no desired product was observed (Scheme 5.12). 

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